RELEASE DATE:  June 20, 2003

PA NUMBER:  PA-03-143

March 2, 2006 (NOT-OD-06-046) – Effective with the June 1, 2006 submission date, 
all R03, R21, R33 and R34 applications must be submitted through Grants.gov using 
the electronic SF424 (R&R) application. Replacement R01 (PA-06-333) and 
R21 (PA-06-334) funding opportunity announcements have been issued for the 
submission date of June 1, 2006 and submission dates thereafter.

EXPIRATION DATE:  April 1, 2006

National Institute of Mental Health (NIMH)



o  Purpose of the PA
o  Research Objectives
o  Mechanism(s) of Support
o  Eligible Institutions
o  Individuals Eligible to Become Principal Investigators
o  Where to Send Inquiries
o  Submitting an Application
o  Peer Review Process
o  Review Criteria
o  Award Criteria
o  Required Federal Citations


This PA replaces PA-00-074.

The National Institute of Mental Health (NIMH) invites research grant 
applications on women's mental health and sex/gender differences in mental 
health across the lifespan.  The overall prevalence of mental disorders does not 
differ between the sexes, but females and males differ in the prevalence and 
clinical course of specific disorders.  Starting in childhood, females have 
twice the incidence of anxiety disorders as do males, who have three times the 
incidence of autism and attention deficit disorder.  After puberty, females 
report twice the incidence of depressive disorders and eight to ten times the 
incidence of eating disorders as do males, who report twice the incidence of 
substance use disorders.  For other serious mental disorders, such as 
schizophrenia and bipolar disorder, gender disparities in incidence are not 
found.  However, significant differences in clinical course have been 
demonstrated across the lifespan.  This pattern of disparities in the 
epidemiology of mental disorders in males and females provides indirect 
evidence of hormonal, biological, social, cultural and developmental factors in 
etiology and course.  An increasing body of basic and clinical research also 
provides evidence of neurobiological sex differences that may predispose to 
clinical differences in mental disorders.  The finding of sex/gender differences 
in epidemiological, basic, and clinical studies has also increased interest in 
the application of that knowledge to improving interventions and services for 
males and females.  In recognition of the importance of studying sex/gender 
differences in health outcomes, NIH has provided guidelines to researchers for 
inclusion of women and men in clinical research and for gender analysis of 
clinical trials outcomes.  Through research such as that called for in this PA, 
NIMH seeks to increase the understanding of the significance of sex/gender 
differences in mental health outcomes and to assess their significance for 
mental health prevention, treatment and services.


In April 2001, the Institute of Medicine issued a report entitled "Exploring 
the Biological Contributions to Human Health:  Does Sex Matter?"  In order to 
improve conceptual research models, the report recommended greater precision in 
terminology used to refer to findings from studies comparing health outcomes in 
males and females.  Therefore, in this PA, the term "sex difference" is used to 
refer to primarily biological variables and the term "gender difference" is 
used to refer to psychosocial and cultural variables.  Nonetheless, it is 
recognized that this distinction is often not clear-cut in the area of brain 
research, where it has been demonstrated that experience can modify brain 
structure and function.

This program announcement identifies three major areas for research emphasis:  
basic and clinical neuroscience; epidemiology and risk factors; and 
intervention and services research.

1) Basic and Clinical Neuroscience - There is increasing evidence that 
neurobiological sex differences impact a wide array of behaviors and may alter 
vulnerability to different mental disorders, severity of course, and/or response 
to different treatments.  Basic studies in animals and humans as well as human 
clinical studies in subjects with mental disorders are appropriate for 
developing knowledge of the processes responsible for these sex differences.

Examples of research areas include studies of:

o  Sex differences in brain processes contributing to behavior as determined by 
structural and functional brain imaging of normative and clinical populations.

o  Sex differences in the molecular and cellular bases of behavior, including 
neurotransmitter and peptide signaling, synaptic plasticity, neurogenesis, and 
regulation of neural circuitry regulating cognition and mood.

o  Sex differences in gene regulatory factors and gene-environment interactions 
contributing to mental disorders.

o  Sex differences in the developmental-organizing and activating influences of 
sex steroids on brain and behavior and their interactions with thyroid- and 
hypothalamic-pituitary adrenal axes, the neuroimmune system, and 
neurotransmitters and peptides in brain.

o  Sex differences and sex hormone influences on the pharmacokinetics, 
pharmacodynamics and pharmacogenetics of psychotropic medications

o  Development of models to examine the impact of hormonal transitions across 
the lifespan on brain function, including, for example, brain plasticity, 
cognition, and mood

Evidence suggests that sex differences in hormone actions contribute to 
differences in physiological and behavioral responses to stress.  There are 
also sex/gender differences in the types of stressors an individual is likely 
to be exposed to.  For example, epidemiological studies show that females are 
more likely to have experienced early childhood sexual abuse, a severe stress 
with potential long-term impact on stress responsiveness.  To understand this 
complex area, multi-disciplinary approaches are required, ranging from basic 
research models in animals and humans to clinical research in children, adults, 
and the elderly.

Examples of relevant research areas include:

o  Examination of brain mechanisms mediating sex differences in the impact of 
stress on appetite, aggression, cognition, exploration, sleep, energy, mood, 
biological rhythms, and susceptibility to mental disorders

o  Elucidation of how biological sex impacts developmental mechanisms 
determining susceptibility to adverse consequences of stress and risk for 
mental disorders throughout life.

2) Epidemiology and Risk Factors - During the past two decades, advances in 
diagnosis and in survey methodologies have enabled researchers to establish 
general estimates of the impact of mental disorders in women and men and their 
intervention and service needs.  This work remains to be done for children and 
adolescents.  The need for such research is particularly pressing, because in 
many disorders, gender differences emerge first in adolescence when early 
intervention strategies may be most effective in preventing full-blown mental 
disorders.  There is also relatively little information about the influence of 
gender-related or gender-specific factors on such important clinical aspects of 
mental disorders as risk for recurrence, chronicity, comorbidity and disability 
in later life.  Studies to further elucidate the role of gender-related or 
gender-specific factors in diagnosis, epidemiology, risk for onset or 
recurrence, and in the course of mental disorders across the lifespan are 

Examples of relevant research areas include:

o  Elucidation of disparities in prevalence of mental illness and related 
disability, and in access to care among women and girls of different ethnic and 
socioeconomic backgrounds.

o  Assessment of the reliability, validity and predictive value of approaches 
to conceptualizing and measuring psychopathology in female populations.

o  Identification of demographic variables and social, cultural, and 
environmental factors related to gender differences in mental disorders (e.g., 
work and family roles, marriage, gender discrimination, response to psychosocial 
stressors, propensity to use substances).

o  Elucidation of childhood risk and protective factors related to the 
emergence of gender disparities in incidence and course of mental disorders 
(particularly mood, anxiety, and eating disorders).

The following lifespan developmental issues are of interest:

o  The roles of hormonal, genetic, and social factors in the emergence of 
sex/gender differences in susceptibility to mental disorders, mood, and 
cognitive disruption during defined transitional periods including puberty, 
pregnancy, the postpartum period, and perimenopause.

3) Intervention and Services Research - There are an increasing number of 
findings indicating sex/gender differences in response to interventions as well 
as in preferences for different kinds of services and interventions.  
Additionally, women's social roles and reproductive status raise special issues 
related to choices of treatments and services.  Interventions are defined here 
to include preventive, treatment, services-system and rehabilitative strategies 
at the individual, provider, organizational and systems levels.  There is a 
need to incorporate consideration of such issues in the design and analysis of 
outcomes in mental health research.

Examples of relevant research areas include studies of:

o  Sex/gender differences in acute and maintenance treatment outcomes for mental 
disorders and suicidal behaviors.

o  Sex/gender differences in treatment adherence and side effects of treatments 
and in treatment preferences, expectancies, provider behaviors, and services 

o  Drug-drug interactions (e.g., supplements, replacement hormones, and 
psychotropic and other medications) in females across the life span.

o  Strategies for early detection of precursors to depression, anxiety, eating 
disorders, suicidality, and other behavioral disorders in female children and 
adolescents; the development of interventions targeting these manifestations; 
and the development of effective mechanisms for successful referral and 
adherence to treatment.

o  Interventions aimed at improving outcomes in women and girls at risk for mental 
disorders or diagnosed with mental disorders comorbid with other disorders (e.g., 
anxiety disorders in depression; substance abuse in women with bipolar disorder or 
schizophrenia, depression, and medical illness).

o   Preventive interventions for mental disorders with female-specific risk 
factors (e.g., stressors in caregiver roles, etc.).

o  Taxonomies of functional outcomes and disabilities in women and girls with 
mental disorders and instruments to measure functional changes following 

o  Screening and identification of women with mental disorders and of women who 
are at high risk for the development of such disorders in general medical 
settings and in non-traditional settings, with the development of effective 
strategies for referral and treatment.


This PA uses the NIH Research Project Grant (R01), Exploratory/Developmental 
Grant (R21), Clinical Trial Planning Grant (R34), and Small Grant (R03) award 
mechanisms.  As an applicant, you will be solely responsible for planning, 
directing, and executing the proposed project.  The total project period for 
an R01 application submitted in response to this PA may not exceed five years.

The Small Grant (R03) provides two years of funding with a maximum of $50,000 
direct costs for each year.  Instructions for the R03 application can be found 
at (https://grants.nih.gov/grants/guide/pa-files/PA-03-108.html).  The 
Exploratory/ Developmental Grant (R21) provides two years of funding with a 
maximum of $275,000 direct costs for each year over the entire budget period; 
with no one year exceeding $200,000.  It is intended for development and pilot 
testing of novel models and sensitive neurochemical measurements.

The R34 mechanism provides up to $450,000 direct costs for three years with no 
one year exceeding $225,000 for research on 1) the development and/or pilot 
testing of new or adapted interventions, 2) pilot testing interventions with 
demonstrated efficacy in broader scale effectiveness trials, or 3) innovative 
services research directions that require preliminary testing or development.  
Instructions for R21 applications can be found at 

This PA uses just-in-time concepts.  It also uses the modular as well as the non-
modular budgeting formats (see 
https://grants.nih.gov/grants/funding/modular/modular.htm).  Specifically, if 
you are submitting an application with direct costs in each year of $250,000 or 
less, use the modular format.  Otherwise follow the instructions for non-modular 
research grant applications.  This program does not require cost sharing as 
defined in the current NIH Grants Policy Statement at 


You may submit (an) application(s) if your institution has any of the following 

o  For-profit or non-profit organizations
o  Public or private institutions, such as universities, colleges, hospitals, 
and laboratories
o  Units of State and local governments
o  Eligible agencies of the Federal government
o  Domestic or foreign
o  Faith-based or community-based organizations


Any individual with the skills, knowledge, and resources necessary to carry out 
the proposed research is invited to work with their institution to develop an 
application for support.  Individuals from underrepresented racial and ethnic 
groups as well as individuals with disabilities are always encouraged to apply 
for NIH programs.


We encourage your inquiries concerning this PA and welcome the opportunity to 
answer questions from potential applicants.  Inquiries may fall into two areas:  
scientific/research and financial or grants management issues:

o  Direct your questions about scientific/research issues to:

Mary C. Blehar, Ph.D.
Director, Women's Mental Health Program
National Institute of Mental Health
6001 Executive Boulevard, Room 8125, MSC 9659
Bethesda, MD  20892-9659
Telephone:  (301) 443-2847
FAX:  (301) 443-8552
Email:  mblehar@mail.nih.gov

o  Direct your questions about financial or grants management matters to:

Joy R. Knipple
Grants Management Branch
National Institute of Mental Health
6001 Executive Boulevard, Room 6115, MSC 9605
Bethesda, MD  20892-9605
Telephone:  (301) 443-8811
FAX:  (301) 443-6885
Email:  jk173@nih.gov


Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001).  The PHS 398 is available at 
https://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive 
format.  For further assistance contact GrantsInfo, Telephone (301) 710-0267, 
Email: GrantsInfo@nih.gov.

APPLICATION RECEIPT DATES:  Applications submitted in response to this program 
announcement will be accepted at the standard application deadlines, which are 
available at https://grants.nih.gov/grants/dates.htm.  Application deadlines are 
also indicated in the PHS 398 application kit.

up to $250,000 per year in direct costs must be submitted in a modular grant 
format.  The modular grant format simplifies the preparation of the budget in 
these applications by limiting the level of budgetary detail.  Applicants 
request direct costs in $25,000 modules.  Section C of the research grant 
application instructions for the PHS 398 (rev. 5/2001) at 
https://grants.nih.gov/grants/funding/phs398/phs398.html includes step-by-step 
guidance for preparing modular grants.  Additional information on modular 
grants is available at https://grants.nih.gov/grants/funding/modular/modular.htm.

Applications requesting $500,000 or more in direct costs for any year must 
include a cover letter identifying the NIH staff member within one of NIH 
institutes or centers who has agreed to accept assignment of the application.

Applicants requesting more than $500,000 must carry out the following steps:

1) Contact the IC program staff at least 6 weeks before submitting the 
application, i.e., as you are developing plans for the study; 

2) Obtain agreement from the IC staff that the IC will accept your application 
for consideration for award; and,
3) Identify, in a cover letter sent with the application, the staff member and 
IC who agreed to accept assignment of the application.

This policy applies to all investigator-initiated new (type 1), competing 
continuation (type 2), competing supplement, or any amended or revised version 
of these grant application types.  Additional information on this policy is 
available in the NIH Guide for Grants and Contracts, October 19, 2001 at 

SENDING AN APPLICATION TO THE NIH:  Submit a signed, typewritten original of 
the application, including the checklist, and five signed photocopies in one 
package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)

APPLICATION PROCESSING:  Applications must be mailed on or before the receipt 
dates described at https://grants.nih.gov/grants/funding/submissionschedule.htm.  
The CSR will not accept any application in response to this PA that is 
essentially the same as one currently pending initial review unless the 
applicant withdraws the pending application.  The CSR will not accept any 
application that is essentially the same as one already reviewed.  This does 
not preclude the submission of a substantial revision of an application already 
reviewed, but such application must include an Introduction addressing the 
previous critique.

Although there is no immediate acknowledgement of the receipt of an application, 
applicants are generally notified of the review and funding assignment within 8 


Applications submitted for this PA will be assigned on the basis of established 
PHS referral guidelines.  An appropriate scientific review group convened in 
accordance with the standard NIH peer review procedures 
(http://www.csr.nih.gov/refrev.htm) will evaluate applications for scientific 
and technical merit.

As part of the initial merit review, all applications will:

o  Receive a written critique
o  Undergo a selection process in which only those applications deemed to have 
the highest scientific merit, generally the top half of applications under 
review, will be discussed and assigned a priority score
o  Receive a second level review by the appropriate national advisory council or 


The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  In the 
written comments, reviewers will be asked to discuss the following aspects of 
the application in order to judge the likelihood that the proposed research 
will have a substantial impact on the pursuit of these goals:

o  Significance
o  Approach
o  Innovation
o  Investigator
o  Environment

The scientific review group will address and consider each of these criteria in 
assigning the application's overall score, weighting them as appropriate for 
each application.  The application does not need to be strong in all categories 
to be judged likely to have major scientific impact and thus deserve a high 
priority score.  For example, an investigator may propose to carry out important 
work that by its nature is not innovative but is essential to move a field 

SIGNIFICANCE:  Does this study address an important problem? If the aims of the 
application are achieved, how will scientific knowledge be advanced? What will 
be the effect of these studies on the concepts or methods that drive this field?

APPROACH:  Are the conceptual framework, design, methods, and analyses 
adequately developed, well-integrated, and appropriate to the aims of the 
project? Does the applicant acknowledge potential problem areas and consider 
alternative tactics?

INNOVATION:  Does the project employ novel concepts, approaches or methods? Are 
the aims original and innovative? Does the project challenge existing paradigms 
or develop new methodologies or technologies?

INVESTIGATOR:  Is the investigator appropriately trained and well suited to 
carry out this work? Is the work proposed appropriate to the experience level 
of the principal investigator and other researchers (if any)?

ENVIRONMENT:  Does the scientific environment in which the work will be done 
contribute to the probability of success? Do the proposed experiments take 
advantage of unique features of the scientific environment or employ useful 
collaborative arrangements? Is there evidence of institutional support?  

subjects and protections from research risk relating to their participation in 
the proposed research will be assessed. (See criteria included in the section 
on Federal Citations, below).

to include subjects from both genders, all racial and ethnic groups (and 
subgroups), and children as appropriate for the scientific goals of the research 
will be assessed.  Plans for the recruitment and retention of subjects will 
also be evaluated. (See Inclusion Criteria in the sections on Federal Citations, 

CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH:  If vertebrate animals are to be 
used in the project, the five items described under Section f of the PHS 398 
research grant application instructions (rev. 5/2001) will be assessed.


BUDGET:  The reasonableness of the proposed budget and the requested period of 
support in relation to the proposed research.


Applications submitted in response to a PA will compete for available funds with 
all other recommended applications.  The following will be considered in making 
funding decisions:

o  Scientific merit of the proposed project as determined by peer review
o  Availability of funds
o  Relevance to program priorities


HUMAN SUBJECTS PROTECTION:  Federal regulations (45CFR46) require that 
applications and proposals involving human subjects must be evaluated with 
reference to the risks to the subjects, the adequacy of protection against 
these risks, the potential benefits of the research to the subjects and others, 
and the importance of the knowledge gained or to be gained.

involving Phase I and II clinical trials must include provisions for assessment 
of patient eligibility and status, rigorous data management, quality assurance, 
and auditing procedures.  In addition, it is NIH policy that all clinical 
trials require data and safety monitoring, with the method and degree of 
monitoring being commensurate with the risks (NIH Policy for Data Safety and 
Monitoring, NIH Guide for Grants and Contracts, June 12, 1998: 

NIH that women and members of minority groups and their sub-populations must be 
included in all NIH-supported clinical research projects unless a clear and 
compelling justification is provided indicating that inclusion is inappropriate 
with respect to the health of the subjects or the purpose of the research.  This 
policy results from the NIH Revitalization Act of 1993 (Section 492B of Public 
Law 103-43).

All investigators proposing clinical research should read the "NIH Guidelines 
for Inclusion of Women and Minorities as Subjects in Clinical Research - 
Amended, October, 2001," published in the NIH Guide for Grants and Contracts on 
October 9, 2001 (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02
-001.html); a complete copy of the updated Guidelines are available at 
The amended policy incorporates:  the use of an NIH definition of clinical 
research; updated racial and ethnic categories in compliance with the new OMB 
standards; clarification of language governing NIH-defined Phase III clinical 
trials consistent with the new PHS Form 398; and updated roles and 
responsibilities of NIH staff and the extramural community.  The policy 
continues to require for all NIH-defined Phase III clinical trials that:  
a) all applications or proposals and/or protocols must provide a description of 
plans to conduct analyses, as appropriate, to address differences by sex/gender 
and/or racial/ethnic groups, including subgroups if applicable; and 
b) investigators must report annual accrual and progress in conducting analyses, 
as appropriate, by sex/gender and/or racial/ethnic group differences.

The NIH maintains a policy that children (i.e., individuals under the age of 
21) must be included in all human subjects research, conducted or supported by 
the NIH, unless there are scientific and ethical reasons not to include them.  
This policy applies to all initial (Type 1) applications submitted for receipt 
dates after October 1, 1998.

All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines" on the inclusion of children as participants in 
research involving human subjects that is available at 

requires education on the protection of human subject participants for all 
investigators submitting NIH proposals for research involving human subjects.  
You will find this policy announcement in the NIH Guide for Grants and 
Contracts Announcement, dated June 5, 2000, at 

Office of Management and Budget (OMB) Circular A-110 has been revised to provide 
public access to research data through the Freedom of Information Act (FOIA) 
under some circumstances.  Data that are (1) first produced in a project that 
is supported in whole or in part with Federal funds and (2) cited publicly and 
officially by a Federal agency in support of an action that has the force and 
effect of law (i.e., a regulation) may be accessed through FOIA.  It is 
important for applicants to understand the basic scope of this amendment.  
NIH has provided guidance at 

Applicants may wish to place data collected under this PA in a public archive, 
which can provide protections for the data and manage the distribution for an 
indefinite period of time.  If so, the application should include a description 
of the archiving plan in the study design and include information about this in 
the budget justification section of the application.  In addition, applicants 
should think about how to structure informed consent statements and other human 
subjects procedures given the potential for wider use of data collected under 
this award.

Department of Health and Human Services (DHHS) issued final modification to 
the "Standards for Privacy of Individually Identifiable Health Information", 
the "Privacy Rule," on August 14, 2002.  The Privacy Rule is a federal 
regulation under the Health Insurance Portability and Accountability Act 
(HIPAA) of 1996 that governs the protection of individually identifiable 
health information, and is administered and enforced by the DHHS Office for 
Civil Rights (OCR). Those who must comply with the Privacy Rule (classified 
under the Rule as "covered entities") must do so by April 14, 2003  (with the 
exception of small health plans which have an extra year to comply).  

Decisions about applicability and implementation of the Privacy Rule reside 
with the researcher and his/her institution. The OCR website 
(http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including 
a complete Regulation Text and a set of decision tools on "Am I a covered 
entity?"  Information on the impact of the HIPAA Privacy Rule on NIH 
processes involving the review, funding, and progress monitoring of grants, 
cooperative agreements, and research contracts can be found at 

URLs IN NIH GRANT APPLICATIONS OR APPENDICES:  All applications and proposals 
for NIH funding must be self-contained within specified page limitations.  
Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) 
should not be used to provide information necessary to the review because 
reviewers are under no obligation to view the Internet sites.  Furthermore, we 
caution reviewers that their anonymity may be compromised when they directly 
access an Internet site.

HEALTHY PEOPLE 2010:  The Public Health Service (PHS) is committed to achieving 
the health promotion and disease prevention objectives of "Healthy People 2010," 
a PHS-led national activity for setting priority areas.  This PA is related to 
one or more of the priority areas.  Potential applicants may obtain a copy of 
"Healthy People 2010" at http://www.health.gov/healthypeople.

AUTHORITY AND REGULATIONS:  This program is described in the Catalog of Federal 
Domestic Assistance at http://www.cfda.gov/ and is not subject to the 
intergovernmental review requirements of Executive Order 12372 or Health Systems 
Agency review.  Awards are made under the authorization of Sections 301 and 405 
of the Public Health Service Act as amended (42 USC 241 and 284)and administered 
under NIH grants policies described at 
https://grants.nih.gov/grants/policy/policy.htm and under Federal Regulations 
42 CFR 52 and 45 CFR Parts 74 and 92.  All awards are subject to the terms and 
conditions, cost principles, and other considerations described in the NIH 
Grants Policy Statement.  The NIH Grants Policy Statement can be found at 

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and discourage the use of all tobacco products.  In addition, Public 
Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain 
facilities (or in some cases, any portion of a facility) in which regular or 
routine education, library, day care, health care, or early childhood 
development services are provided to children.  This is consistent with the PHS 
mission to protect and advance the physical and mental health of the American 

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices

Office of Extramural Research (OER) - Home Page Office of Extramural
Research (OER)
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Bethesda, Maryland 20892
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